Abstract
A cover for a fluid container having an essentially plane cover plate for closing at least one opening of at least one fluid container and at least two ports, and each port has a through channel extending through the entire thickness of the cover plate and a fluid impermeable first membrane is arranged over the entire cross section of the through channel of the first port and an at least gas permeable second membrane is arranged over the entire cross section of the through channel of the second port is disclosed.
Claims
1. A cover (1) for a fluid container (4) comprising an essentially plane cover plate (10) for closing at least one opening of at least one fluid container (4) and at least two ports (11,12), wherein each port (11,12) comprises a trough channel (110,120) extending through the entire thickness of the cover plate (10), characterized in that a fluid impermeable first membrane (2) is arranged over the entire cross section of the through channel (110) of the first port (11) and in that an at least gas permeable second membrane (3;30) is arranged over the entire cross section of the through channel (120) of the second port (12).
2. The cover (1) according to claim 1, wherein the second membrane (30) is permeable for gas and liquid.
3. The cover (1) according to claim 1, wherein a collar (121) is provided on the circumference of the second port (12) on an outer side of the cover plate (10), extending essentially perpendicular to the cover plate (10).
4. The cover (1) according to claim 3, comprising a fastening element provided on the exterior surface of the collar (121) of the second port (12).
5. The cover (1) according to claim 1, comprising a third port (13) with a through channel (130), extending through the entire thickness of the cover plate (10), wherein the third port (13) is membrane-free.
6. The cover (1) according to claim 5, wherein a collar (131) is provided on the circumference of the third port (13) on an outer side of the cover plate (10), extending essentially perpendicular to the cover plate (10).
7. The cover (1) according to claim 6, comprising a fastening element provided on the exterior surface of the collar (131) of the third port (13).
8. The cover (1) according to claim 1, wherein a holding plate (16) is arranged on the inner side of the cover plate (10), wherein the membranes (2,3;30) are clamped between the cover plate (10) and the holding plate (16) and wherein the holding plate (16) comprises through channels (160,161,162) that are aligned with the corresponding through channels (110,120,130) of the cover plate (10).
9. The cover (1) according to claim 8, wherein the diameter of each through channel (160,161,162) of the holding plate (16) is the same size as or is smaller than the corresponding diameter of the through channel (110,120,130) of the cover plate (10).
10. The cover (1) according to claim 8, wherein a shoulder (1600) is formed in the through channel (160) of the holding plate (16), on a channel end which is facing the cover plate (10).
11. The cover (1) according to claim 8, wherein a funnel (1610) is formed in the through channel (161) of the holding plate (16) that is aligned with the through channel (120) of the second port (12) of the cover plate (10), on a channel end which is facing the cover plate (10).
12. The cover (1) according to claim 8, wherein an aspiration tube (14) is provided on a side of the holding plate (16) facing away from the cove plate (10), extending from the holding plate (16), forming an extension of the through channel (160) of the holding plate (16) that is aligned with the through channel (110) of the first port (11) of the cover plate (10).
13. The cover (1) according to claim 12, wherein at least one recess (140) is formed in the aspiration tube (14) on its free end facing away from the holding plate (16).
14. The cover (1) according to claim 1, comprising a closed side wall (15;151) which extends a multiple of the thickness of the cover plate (10) from the circumference of the cover plate (10).
15. The cover (1) according to claim 14, comprising a fastening element (150) provided on the inward facing surface of the side wall (15).
16. The cover (1) according to claim 1, comprising one first port (11) and two or more second ports (12), wherein the two or more second ports (12) are identical or different.
17. The cover (1) according to claim 16, wherein a gas permeable second membrane (3) is arranged in at least one of the second ports (12) and wherein a gas and liquid permeable second membrane (30) is arranged in at least one of the second ports (12).
18. The cover (1) according to claim 1, wherein several first ports (11) and several second ports (12) and/or several third ports (13) are arranged on a common cover plate (10).
19. A set comprising a cover (1) according to claim 1 and at least one fluid container (4), wherein the cover (1) is arranged as such that it completely covers at least one opening of the at least one fluid container (4).
20. A filling quantity measurement arrangement comprising a reception (8), a fluid container (4) with a cover (1) according to claim 12 and an evaluation unit (9), wherein the aspiration tube (14) of the cover (1) reaches into the container (4), wherein the evaluation unit (9) is electro conductively connected to the aspiration tube (14) and the reception (8), and wherein the evaluation unit (9) is adapted to determine the filling quantity in the container (4) based on the measured capacitance between the reception (8) and the aspiration tube (14).
21. A method for determining the filling quantity of a fluid container (4), comprising the steps of: providing a reception (8) for a non-conductive fluid container (4) and an evaluation unit (9) that is electro conductively connected to the reception (8); arranging a non-conductive fluid container (4) in the reception (8), wherein a cover (1) according to claim 14 is arranged on the fluid container (4), wherein the aspiration tube (14) of the cover (1) reaches into the container (4); connecting electro conductively the evaluation unit (9) with the aspiration tube (14); measuring the capacitance between the reception (8) and the aspiration tube (14); determining the filling quantity of the fluid container (4) by evaluating the measured capacitance.
22. A method of pipetting a fluid, comprising the following steps: providing a cover (1) according to claim 1 and at least one fluid container (4), wherein the cover (1) is arranged as such that it completely covers at least one opening of the at least one fluid container (4), inserting an aspirator (6) or a dispenser (5) into the at least one fluid container (4) by piercing the fluid-impermeable first membrane (2), and pipetting a fluid into the fluid container (4) or out of the fluid container (4) using the aspirator (6) or the dispenser (5) without removing the cover (1) from the at least one fluid container (4).
23. The method according to claim 22, wherein the fluid is dispensed into the fluid container (4) using a second port (12) or a third port (13), and/or wherein the fluid is aspirated from the fluid container (4) using the first port (11) and/or the third port (13).
24. The method according to claim 22, wherein the aspirator (6) is selected from a group comprising a fixed pipette tip and a disposable pipette tip, and wherein the dispenser (5) is selected from a group comprising a fixed pipette tip and a disposable pipette tip.
25. The method according to claim 22, wherein the pipetting of a fluid is under the control of liquid handling device (17), the liquid handling device (17) being selected from a group comprising an automated liquid handling workstation and a handheld pipette.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0085] Embodiments of the current invention are described in more detail in the following with reference to the figures. These are for illustrative purposes only and are not to be construed as limiting. It shows
[0086] FIG. 1 a perspective view from above of a cover according to the invention, arranged above a container;
[0087] FIG. 2 a perspective view from below of the free end of the aspiration tube of the cover from FIG. 1;
[0088] FIG. 3A a perspective view from above of a minimal embodiment of a cover according to the invention;
[0089] FIG. 3B a perspective view from below of the cover from FIG. 3A;
[0090] FIG. 4 a section view of the cover of FIGS. 3A and 3B through its first and second port;
[0091] FIG. 5 a section view of the cover of FIG. 1 through its first, second and third port;
[0092] FIG. 6 a perspective exploded view of the cover of FIG. 1;
[0093] FIG. 7 a section view of the holding plate of FIGS. 5 and 6;
[0094] FIG. 8 a perspective view from above of the cover of FIG. 1 with an aspirator arranged above the first port, with dispenser arranged at the second port and with a filter arranged at the third port;
[0095] FIG. 9 a section view of the cover of FIG. 1 on a container, arranged in a reception;
[0096] FIG. 10 a section view of a plug-type cover through its first, second and third port;
[0097] FIG. 11 a perspective explosion view from above of a multi-chamber container with a corresponding cover;
[0098] FIG. 12 a perspective explosion view from above of a multi-chamber container with an alternative embodiment of a corresponding cover;
[0099] FIG. 13 a perspective view of a liquid handling device functionally connected to liquid container by a corresponding cover, and
[0100] FIG. 14 a schematic diagram of method steps of pipetting a fluid.
DETAILED DESCRIPTION OF THE INVENTION
[0101] FIG. 1 shows a perspective view from above of a cover 1 according to the invention, arranged above a container 4. The cover comprises an essentially plane cover plate 10, that extends over the entire cross-section of the opening of the container 4. A first port 11 is arranged in the center of the cover plate 10 that has a shape of a circular disk. The opening of the first port 11 is completely closed by a non-permeable first membrane 2. The depicted first membrane is a pierceable septum. Adjacent to the first port 11, two second ports 12 are arranged. In this figure, the second port 12 on the right comprises a collar 121. The second port 12 in the back is collarless. The opening of the second port 12 in the back is completely closed by a gas-permeable second membrane 3. The opening of the second port 12 on the right, although not shown in this figure, is completely closed by a gas and liquid permeable second membrane 30. Adjacent to the first port 11, a third port 13 is arranged. A closed side wall 15 extends from the circumference of the cover plate 10 on the opposite side of the ports 11,12,13 over a multiple of the thickness of the cover plate 10 in the direction of a central axis A. Aligned with the first port 11, a aspiration tube 14 is provided on the side of the cover plate 10, opposite to the ports 11,12,13. The aspiration tube 14 extending over a multiple of the height of the side wall 15 of the cover 1, along the central axis A. Recesses 140 are formed on the free end of the aspiration tube 14, facing away from the cover plate 10, as depicted in FIG. 2. There are four recesses 140 equally distributed around the circumference of the free end of the aspiration tube 14.
[0102] FIG. 3A shows a perspective view from above of a minimal embodiment of a cover 1 according to the invention, FIG. 3B shows a perspective view from below thereof and FIG. 4 shows a section view of the cover through its first and second ports 11,12. In this embodiment, the cover comprises a cover plate 10 with a first port 11 and a second port 12. The first membrane 2 completely closes the opening of the first port 11, i.e. the first membrane 2 is arranged over the whole width of the through channel 110 of the first port 11. The first membrane 2 is arranged on a shoulder 111 in a recess of the cover plate 10. The first membrane 2 can be glued to the shoulder 111. The recess or the shoulder 111 being accessible from the outside of the cover 1. A second membrane 3 completely closes the opening of the second port 12, i.e. the second membrane 3 is arranged over the whole width of the through channel 120 of the second port. The second membrane 3 being arranged on the inside of the cover plate 10. The second membrane 3 can be attached to the inside of the cover plate 10 by vibration welding. A thread 150 is provided on the inside of the closed side wall 15 enabling the cover 1 to be screwed on a container with a complementary thread.
[0103] FIG. 5 a section view of the cover 1 of FIG. 1 through its first port 11, its second port 12 and its third port 13, i.e. through the plane P of FIG. 1. FIG. 6 shows a perspective exploded view of the cover 1 of FIG. 1. In contrast to FIG. 1, in FIG. 5, the cover 1 is arranged on the container 4. In the depicted embodiment, the cover plate 10 extends over the entire width of the container's opening. The side wall 15 extends from the cover plate 10 slightly slanted with respect to the axis A so that the inside diameter of the cover 1 near the lower rim of the side wall 15 is bigger than the one near the cover plate 10. In this embodiment, the fastening element 150 is a latch that can be mated with a corresponding latch of the container 4. At the first port 11, the first membrane 2 is arranged on the inside of the cover plate 10, extending over the entire diameter of the through channel 110. The first membrane 2 is disk-shaped and is pressed against a circumferential rim of the through channel 110 of the first port 11, located at the inside of the cover plate 10. A second port 12 is formed in the cover plate 10 adjacent to the first port 11. The second port 12 comprising a through channel 120 that extends over the whole thickness of the cover plate 10. On the outside of the cover 1, a collar 121 extends from the cover plate 10 towards the outside, said collar 121 being formed integrally with the cover plate 10.
[0104] The outside surface and the inside surface of the collar 121 are tapered as such that the outside diameter of the collar is getting smaller with an increasing distance from the cover plate 10 and the inside diameter of the collar is getting bigger with an increasing distance from the cover plate 10. On the inside of the collar 121, a shoulder is formed, wherein the surface of the shoulder is flush with the outside surface of the cover plate 10. There is a third port 13 arranged adjacent to the first port 11, opposite to the second port 12. The third port 13 comprising a through channel 130 that extends over the entire thickness of the cover plate 10. On the outside of the cover 1, a collar 131 extends from the cover plate 10 towards the outside, said collar 131 being part of a pipe that extends through the cover plate 10. The pipe extends over the inside surface of the cover plate 10, forming a circumferential rim. On the outside surface of the collar 131 of the third port 13, a thread 132 is formed integrally with the collar 131. The third port 13 can be compatible with a Luer-lock-system. On the inside of the cover 1 a holding plate 16 is arranged, fixing the first membrane 2 and the second membrane 3 to the inside of the cover plate 10. The first membrane 2 is arranged in a recess 1600 of the holding plate 16. The second membrane 3 is an annular disc, essentially covering the inside surface of the cover plate 10. There is a cut-out in the second membrane 3, in the region of the third port 13.
[0105] FIG. 7 shows a section view of the holding plate 16 of FIGS. 5 and 6. The holding plate 16 is disk-shaped and comprises a centric first through channel 160, a second through channel 161 adjacent to it and a third through channel 162 adjacent to the first through channel 160, opposite to the second through channel 161. On the side of the holding plate 16 fading the cover plate 10, a recess in the form of a shoulder 1600 is formed the circumference of the first through channel 160. On the same side of the holding plate 16, a funnel-shaped cut-out 1610 is formed at the circumference of the second through channel 161. On the opposite side of the holding plate 16, an aspiration tube 14 is formed integrally with the holding plate 16, extending away from the holding plate 16 in the direction of the axis A.
[0106] FIG. 8 shows a perspective view from above of the cover 1 of FIG. 1 with an aspirator 6 arranged above the first port 11, with dispenser 5 arranged at the second port 12 and with a filter 7 arranged at the third port 13 wherein the aspirator 6 is an aspiration needle and the dispenser 5 is a pipette. The filter 7 is screwed to the cover 1 at the third port 13. The aspirator 6 is fluidly connected to a liquid handling device 17, as well as the dispenser 5. In each case, a pipette of a liquid handling device 17 is indicated by dashed lines.
[0107] FIG. 9 shows a section view of the cover 1 of FIG. 1 on a container 4, arranged in a reception 8. The container 4 being inserted into the reception 8 up to the cover 1, just below the lower rim of the side wall 15. The aspiration tube 14 is electro conductively connected to an evaluation unit 9, which is also electro conductively connected to the reception 8. The aspiration tube 14 represents the first electrode and the reception 8 represents the counter electrode. The liquid volume in the container can be determined by the evaluation unit 9 based on the measured electric capacitance between the aspiration tube 14 and the reception.
[0108] FIG. 10 shows a section view of a plug-type cover 1 through its first port 11, its second port 12 and its third port 13. The depicted cover is a plug-type cover that is adapted to be plugged into the opening of a container 4. In contrast to the cap-type cover of FIGS. 1 and 3 to 6, the side wall 151 of the plug-type cover, in the assembled state, is arranged on the inside of the container 1, i.e. in a chamber 40 of the container. The outside surface of the side wall 151 of the cover 1 matches the inside surface of the chamber 40 of the container 4. Apart from the side wall, the plug-type cover is identical to the cap-type cover.
[0109] FIG. 11 shows a perspective explosion view from above of a container 4 with a plurality of chambers 40 with a corresponding cover 1. Depicted is a multi-well plate 4 with six wells 40. Alternatively, a rack can be used, in which a plurality of containers can be arranged. In both embodiments, a multi cover as shown in FIG. 11 can be used to cover tightly all of the chambers of the container or containers. Such a cover 1 comprises a common cover plate 10, wherein a plurality of first ports 11 with first membranes 2 and a plurality of second ports 12 with second membranes 3 are arranged as such that in the assembled state, the ports 11,12 are aligned with the corresponding chambers 40. Around each group of ports, corresponding to a chamber, on the inside surface of the cover plate 10, a side wall 151 extends away from the cover plate 10 into each chamber. Thus, all chambers are sealed-off from one another. Of course, all embodiments in connection with the cap-type cover can be realized as well with the multi cover 1. Instead of having the side wall 151, it would be possible to have a sealing ridge, extending from the cover plate. In this case, the sealing can take place in the opening region, i.e. the opening edge of each chamber or the sealing can take place on the common top surface of all chambers.
[0110] FIG. 12 shows a perspective explosion view from above of a container 4 with a plurality of chambers 40 with an alternative embodiment of the cover 1 as it is shown in FIG. 11. In this embodiment, the cover comprises in addition to the plurality of first ports 11 and second ports 12 a plurality of additional third ports 13. In this case, the third ports 13 comprise in each case a collar 131 with a thread 132 for connecting for example via the Luer-lock system a sterile filter, for example.
[0111] It may be provided that a plurality of chambers 40 are connected with functionally specific covers 1 to generate a type of micro-bioreactor as mentioned above. It may for example be provided that the ports and membranes of each of the covers 1 differ to provide a specific reaction sequence, and to provide a functionally adapted fluid connection in the desired sequence.
[0112] FIG. 13 shows a perspective view of a liquid handling device 17 functionally connected to a fluid container 4 by a corresponding cover 1. A pipette tip, for example an aspirator or a dispenser, is inserted through the cover 1 into an aspiration tube 14 (dashed lines in the inner of the fluid container 4). The cover 1 here further comprises a second port 12 and a third port 13, the third port 13 comprising a part of a Luer-lock system. The fluid container 4 is placed here into a reception 8. It may be provided that the reception 8 is configured as an electro-conductive hollow cylinder, as for example shown in FIG. 9. The fluid container 4 with the reception 8 is positioned on a work surface of the liquid handling device 17. The dispenser 5 and/or an aspirator 6 are movably connected along an y-direction and along an z-direction to a movable pipetting head, which in turn is movable along an x-direction (see left arm of liquid handling device 17). On the right side of the liquid handling device 17, a gripping arm is shown which is movable along the x-direction. In this case, the gripping arm has two gripping fingers which may be movable along an y-direction and a z-direction.
[0113] FIG. 14 shows a schematic diagram of method steps of pipetting a fluid as it may be carried out using a cover according to the invention. The cover may be adapted to the desired method steps which shall be carried out in in the fluid container. Adaptation may concern for example the number and size and type of the ports and associated membranes, presence of an aspiration tube, configuration of the aspiration tube concerning material, length, or position within the fluid container, etc. The cover and the fluid container are assembled to form a set as described above. Afterwards, an aspirator or a dispenser, for example a pipette tip, is inserted into the container through a first or through a third port of the cover, and the fluid may then be pipetted out of the container or into the container.
TABLE-US-00001 REFERENCE SIGNS LIST 1 cover 161 through channel 10 cover plate 1610 funnel 11 first port 162 through channel 110 through channel 2 first membrane 111 shoulder 3 second membrane 12 second port 30 second membrane 120 through channel 4 fluid container 121 collar 40 chamber 13 third port 5 dispenser 130 through channel 6 aspirator 131 collar 7 filter 132 thread 8 reception 14 aspiration tube 9 evaluation unit 140 recess 17 liquid handling device 15 side wall A axis 150 fastening element P plane 151 side wall 16 holding plate 160 through channel 1600 shoulder
